| 1.BackgroundSuicide,not only seriously affects the daily life and spiritual life of family and friends,also brings great burden to society.According to the report by World Health Organization in 2014,over 800,000 people,namely one person every 40 seconds,die by suicide.In China,about 287,000 people die of suicide,2 million people attempt suicide each year.Suicide was ranked as the fifth cause of death among the whole population and first cause of death among the population aged 15 to 34.Suicide is complex and the influence factors are various,mainly involve the sociological factor,the personal characteristic,the psychological factor,the genetic and biological factor,and so on.Among the biological factors,a variety of studies focus on the serotonergic system.Serotonin,also known as 5-hydroxytryptamine(5-HT),is a crucial central neurotransmitter.Experimental studies on suicide have shown that the function of 5-HT in the brain of suicide patients decreases.So the 5-HT system gene becomes one of the important candidate genes to predict the risk of suicide.In recent years,there are many studies on the relationship between suicide and 5-HT system related gene,but the conclusion is different.Therefore,this study selected 4 SNPs of 5-HT system related gene to explore the association between attempted suicide and HTR2A,TPH1 and TPH2 gene polymorphisms in rural China.Suicide attempt is a reliable predictor of suicide death.Studies have shown that people who have attempted suicide are 20 to 30 times more likely to suicide than the general population.About 25 percent of suicide attempters repeated suicide and 10 percent died of suicide.Therefore,this study followed up the subjects to further explore the association between repeated suicidal behaviors and HTR2A,TPH1 and TPH2 gene polymorphisms in rural China.2.Objectives(1)To explore the relationship between 5-HT gene polymorphisms with rural suicide attempt and the higher-order interaction of genetic and environmental factors on suicide attempt.(2)To explore the relationship between 5-HT gene polymorphisms with repeated suicidal behaviors.3.Methods3.1 SubjectsThe subjects of baseline investigation were from a 1:1 case-control study.Cases were who did suicide attempt from October 1,2009 to March 31,2011.They were from six rural counties:Ju'nan,Lijin,Ningyang,Penglai,Tengzhou and Zoucheng and aged 15 to 70.Controls were matched by gender,age(±3 years),residential village,and had no history of suicide.All cases and controls were recruited from rural counties in the hospitalization injury surveillance sites of Shandong Province.In this study,a total of 409 pairs of subjects were collected.The blood samples from 6 cases and 10 control cases were not available.Finally,393 pairs of cases and controls were included.The subjects of follow-up investigation included all the subjects in the initial interview.3.2 Procedure and instrumentsThe investigation was divided into two stages:the initial investigation and the follow-up investigation,both using one-to-one and face-to-face interview by questionnaires.The initial interview lasted about 1.5 hours,and 1ml of venous blood was extracted from the subjects by the village doctor or the staff of the clinical laboratory of the hospital.The follow-up interview was about 0.5 hours,and the missed blood samples were collected.Instruments included demographic characteristics,suicidal behaviors,life event scale,and diagnosis of mental disorders.3.3 Experimental methodDNA was extracted and gene polymorphisms were analyzed by PCR-LDR.3.3 Data processing and analysisDouble data entry was conducted with Epidata software,statistical analysis was conducted with SPSS 24.0 software.The continuous data were compared by t test or analysis of variance.Classification variables,such as the distribution of genotype and allele frequency,and demographic variables,were described by constituent ratio,and compared by chi-square test or Fisher's exact probability method.Hardy-Weinberg equilibrium test was conducted by chi-square test.When the risk factors were analyzed,univariate conditional logistic regression analysis was performed first,and multivariate conditional logistic regression analysis was further performed for the variables with statistical significance.Generalized Multifactor Dimensionality Reduction(GMDR)was used to explore the high-order interaction effect of the factors influencing suicide attempt.The gene score was used to study the accumulative effect of 4 gene loci on suicide attempt.4.Main results4.1 Epidemiological characteristics of suicide attemptersInformation of 393 suicide attempters and 393 controls was collected at last.Among the suicide attempts,265 cases were female,accounting for 67.4%;128 cases were male,accounting for 32.6%.The ratio of male to female among suicide attempters was 1:2.1.The average age of suicide attempts was 43.82113.31 years old.Main method for suicide was oral pesticide(n=328,83.5%)and there was statistically significant difference in the method for suicide between males and females(P=0.038).The mean score of suicide intent was 4.50±2.63,4.42±2.59 for females and 4.68±2.71 for males.There was no significant difference in suicide intent between males and females(P=0.350).There was significant difference in the possibility of intervention in time and no significant difference in the other seven items of suicide intent between men and women.Among all attempted suicides,130(33.1%)had at least one mental illness,79(29.8%)for females and 51(39.8%)for males,and the difference was statistically significant(P=0.048).In the specific four categories of disorders,the prevalence of mood disorders(22.9%)was highest in the general population.The difference of substance use disorder between male and female was statistically significant(23.4%vs.1.1%,P<0.001),and male were significantly more likely than female.There were no significant differences in mood disorder,psychotic disorder and anxiety disorder between males and females.4.2 Environmental factors of suicide attemptThe environmental factors selected in this study were:education level(P<0.001),economic status(P=0.001),family history of suicide(P=0.016),negative life event(P<0.001),pesticide storage at home(P<0.001),physical disease(P=0.005)and mental disease(P<0.001).4.3 Relationship between gene polymorphisms and suicide attemptBy comparing the genotype frequency and allele frequency distribution of each locus,it was found that the difference in the allele frequency distribution of rs4537731 of TPH1 gene was statistically significant(P=0.014),the other 6 loci were insignificant,and there was no statistical difference in genotype frequency distribution of all loci.The genotype frequency distribution of rs6311 between suicide attempters with and without mood disorder was statistically different(P=0.002).There was no statistically significant difference in genotype and allele frequency distribution between suicide attempters with or without psychotic disorder,substance use disorder,anxiety disorder,and between suicide attempts in different suicide methods.There was also no statistically significant difference in genotype and allele frequency distribution between suicide attempts without mental illness and the controls.Only the association between rs4537731 and attempted suicide was significant in univariate conditional logistic regression analysis.Additive model(OiR=1.36,95%CI:1.05-1.74)and dominant model(OR=1.38,95%CI:1.03-1.86)were all significant.After adjusting for meaningful environmental factors,no model showed that rs4537731 was associated with attempted suicide.GMDR analysis also did not find the relationship between rs4537731 and attempted suicide.Moreover,there was no association between gene score and suicide attempt.4.4 Follow-up studyIn the follow-up of 786 subjects at baseline,671 were successfully investigated,including 337 suicide attempts and 334 living controls.During the follow-up,16(4.7%)suicide attempters had repeated behaviors.Among them,there were 7 suicide attempters and 9 suicide deaths.There was statistically significant difference in the occurrence of repetitive behaviors among all genotypes at rs1799913 of TPH1 gene(P=0.043).The repetitive behaviors of genotype AA(2.5%)was less than genotype AC(3.0%)and genotype CC(10.0%).But no difference was found in other gene loci.5.Conclusions(1)Univariate analysis found that only rs4537731 of TPH1 was associated with suicide attempt,but this association disappeared in multivariate analysis.Moreover,there was no association between gene score and suicide attempt.These results did not support the relationship between 5-HT system genes and suicide attempt.(2)During the follow-up,there was statistically significant difference in the occurrence of repetitive behaviors among all genotypes at rsl799913 of TPHI gene,which supported the relationship between rs1799913 of TPH1 gene and repeated suicide. |
PDF Full Text Request